Infective endocarditis (IE) is associated with an in-hospital mortality rate of 15–30%. Standard treatment requires 2 to 6 weeks of intrave-nous (IV) antibiotic therapy, resulting in prolonged hospitalization with its attendant risks, including catheter-related complications, in-creased length of stay, and cost.This review summarizes the current evidence, eligibility criteria, antibiotic regimen selection, and practical aspects of partial oral ibiotic therapy (POAT) for IE. Oral treatment is already recommended for right-sided Staphylococcus aureus IE and IE caused by atypical pathogens. The landmark POET trial (2019) demonstrated the non-inferiority of POAT — initiated after at least 10 days of IV therapy — versus continued IV treatment for left-sided IE caused by streptococci, Enterococcus faecalis, S. aureus, or coagu-lase-negative staphylococci. Long-term follow-up at 5.4 years demon-strated lower all-cause mortality in the POAT group. The 2023 ESC Guidelines now formally endorse POAT for selected patients fulfilling strict criteria. Despite robust evidence, POAT is currently implemented in fewer than half of eligible patients. These findings have since been corroborated by the WikiGuidelines Group consensus statement and the French SPILF-AEPEI position statement, and extended by re-al-world evidence (the ENDO-ORAL study) suggesting that carefully selected patients falling outside strict trial-based eligibility criteria may also benefit from oral step-down therapy. POAT represents a safe, effective, and resource-efficient alternative to prolonged IV therapy in carefully selected patients. Strict adherence to eligibility criteria, ap-propriate antibiotic selection based on pathogen susceptibility, and close clinical follow-up are essential to optimize outcomes.